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BACKGROUND : Anthocyanins, which are found in high concentrations in fruit and vegetable, may play a beneficial role in retarding or reversing the course of chronic degenerative diseases. However, little is known about the biotransformation and the metabolism of anthocyanins so far. AIM OF THE STUDY : The aim of the study was to investigate possible transformation pathways of anthocyanins by human faecal microflora and by rat liver microsomes as a source of cytochrome P450 enzymes as well as of glucuronyltransferases. METHODS : Pure anthocyanins, an aqueous extract of red radish as well as the assumed degradation products were incubated with human faecal suspension. The incubation mixtures were purified by solid-phase extraction and analysed by HPLC/DAD/MS and GC/MS. Quantification was done by the external standard method. Furthermore the biotransformation of anthocyanins by incubation with rat liver microsomes in the presence of the cofactor NADPH (as a model for the phase I oxidation) and in the presence of activated glucuronic acid (as a model for the phase II glucuronidation) was investigated. RESULTS : Glycosylated and acylated anthocyanins were rapidly degraded by the intestinal microflora after anaerobic incubation with a human faecal suspension. The major stable products of anthocyanin degradation are the corresponding phenolic acids derived from the B-ring of the anthocyanin skeleton. Anthocyanins were not metabolised by cytochrome P450 enzymes, neither hydroxylated nor demethylated. However they were glucuronidated by rat liver microsomes to several products. CONCLUSIONS : The gut microflora seem to play an important role in the biotransformation of anthocyanins. A rapid degradation could be one major reason for the poor bioavailability of anthocyanins in pharmacokinetic studies described so far in the literature. The formation of phenolic acids as the major stable degradation products gives an important hint to the fate of anthocyanins in vivo. [ABSTRACT FROM AUTHOR]

Background: The oxidative modification of LDL is considered to play a central role in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Paraoxonase (PON1) protects LDL from oxidation and may therefore retard the developement of atherosclerosis. The PON 1-192 polymorphism is associated with diminished PON1 concentrations and an increased risk for CHD in RR-allele subjects. Aim of the study: To investigate the effect of tomato juice consumption on PON 1 activity and other parameters related to oxidative stress in healthy elderly subjects. Furthermore, the PON 1-192 genotype has been determined in the volunteers in order to see whether possible treatment effects are related to the PON1-192 polymorphism. Methods: Fifty elderly subjects were randomly assigned to control (mineral water) or intervention group (tomato juice). Subjects of the tomato juice group consumed daily 330 mL tomato juice for 8 weeks. Antioxidant status was measured as LDL oxidation, plasma malondialdehyde, ferric reducing ability of plasma (FRAP) and PON 1 activity. The PON 1-192 polymorphism was determined by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). Plasma carotenoids were analyzed by HPLC. Results: Tomato juice consumption reduced LDL-oxidation and improved antioxidant status in R-allele carriers, but not in the QQ genotype group. PON1 activity increased irrespective of the genotype in both, control and intervention group. Conclusions: The changes in antioxidant status after tomato juice consumption seem to depend on the PONI-192 genotype. Healthy elderly, carrying the R-allele, could specificly reduce their higher cardiovascular risk by changing dietary habits. [ABSTRACT FROM AUTHOR]

The article focuses on the International Life Sciences Institute (ILSI), which advances the understanding of scientific issues relating to nutrition, food safety, toxicology, risk assessment and the environment. By bringing together scientists from academia, government, industry, and the public sector, ILSI seeks a balanced approach to solving problems of common concern for the well-being of the general public. ILSI is headquartered in Washington, D.C. ILSI Europe was established in 1986 to identify and evaluate scientific issues related to the above topics through symposia, workshops, expert groups and resulting publications.

BACKGROUND: The role of dietary factors in the aetiology of human cancer is an area, which has attracted intense interest in recent years. The suggestion that approximately one third of all cancers may be caused by an 'inappropriate' balance of food components has led to the attractive contention that we can significantly decrease cancer incidence through dietary recommendations and a change in dietary habits in populations. Thus, a key issue must be to establish clear criteria, which must be met in order to be able to make 'cancer risk reduction' claims for food components. In this area, the one true marker is the malignant human tumour, which for practical reasons is usually not accessible to claims. In its absence, we must rely on alternative markers--biomarkers/surrogate endpoints. This paper mainly deals with the link of these biomarkers to the endpoint tumour and their usefulness for making claims. Some claims have been made based on epidemiological studies. AIM: Can we identify targets/ biomarkers in the chain of events from initial 'exposure' to overt malignant tumour, whose modification can be used to make 'anticancer' claims for food components? RESULTS: We identified 18 targets/markers in the above chain of events whose modification 'have the potential' to be used for 'reduction of cancer risk' claims for food components. These targets/markers fall under 5 broad headings: tumours and preneoplastic changes; cellular targets/markers; gut luminal markers; angiogenesis and metastasis; carcinogen metabolising enzymes; genetic events. CONCLUSIONS: The strongest markers presently available are precancerous lesions (e. g. polyps or aberrant crypt foci) in humans and precancerous lesions and tumours in animal models. The only marker that presently can be used for a 'reduction of disease risk' claim (type B) for food components is 'polyp recurrence'. Type B claims cannot be made on the basis of results in animal models. All of the other biomarkers examined presently lack validation against the 'true endpoint', the tumour, and thus cannot be used for type B claims. 'Reduction of disease risk' claims in the area of 'diet-related cancer' should be based primarily on human intervention studies using relevant/acceptable endpoints. An important area for future research will be the validation of these surrogate endpoints. [ABSTRACT FROM AUTHOR]

Background: Obesity is a chronic sub-inflammatory condition which is a risk factor for several cancer diseases, e.g. colon cancer. Adipose tissue secretes biologically active factors like leptin with a known pro-inflammatory or mitogenic activity. Both, chronic inflammation and an increased cell proliferation are considered to play an important role in colon carcinogenesis. Diverse phytochemicals were shown to have cell growth inhibiting effects., Aim of the Study: The aim was to investigate whether adipocytes could mediate a proliferative capacity to HT29, a human colon adenocarcinoma cell line, and whether phytochemicals could modulate this effect., Methods: Infranatants of adipocyte cultures from different donors were prepared and the effects of those conditioned adipocyte media (CAM) on HT29 cell growth were measured. Additionally, cell cycle progression was analyzed by flow cytometry after CAM treatment and ERK 1/2 phosphorylation was analyzed., Results: CAM from a subgroup of adipose tissue donors stimulated HT29 cell growth, whereas others did not. This effect seems to be mediated via the ERK 1/2 pathway. Furthermore, CAM caused changes in cell cycle distribution with a shift of HT29 cells from G1- into the S-phase. This effect could be mimicked by leptin (1 nM). Co-incubation of CAM-treated HT29 cultures with beta-carotene or EGCG did not have a significant impact on cell cycle progression, whereas genistein (30 microM) tended to inhibit the CAM-stimulated transition of cells into the S-phase., Conclusion: This study confirmed the mitogenic activity of leptin in HT29 cells, although leptin secretion from adipocytes is not likely to be responsible for CAM-stimulated cell growth in our test system. The investigated phytochemicals seem to have only a minor influence on CAM-mediated cell cycle progression.

The carotenoid zeaxanthin accumulates in the human macula lutea and protects retinal cells from blue light damage. However, zeaxanthin intake from food sources is low. Increasing zeaxanthin in common foods such as potatoes by traditional plant breeding or by genetic engineering could contribute to an increased intake of this carotenoid and, consequently, to a decreased risk of age-related macular degeneration. Our aim was to investigate whether zeaxanthin from genetically modified zeaxanthin-rich potatoes is bioavailable in humans. Three men participated in this randomized, controlled double-blinded, crossover pilot study. All subjects consumed 1,100 g of mashed potatoes, either genetically modified (Solanum tuberosum L. var. Baltica GM47/18; 3 mg zeaxanthin) or wild-type control potatoes (Solanum tuberosum L. var. Baltica; 0.14 mg zeaxanthin). A second treatment was followed after a 7-day wash-out period. The concentration of zeaxanthin was significantly increased in chylomicrons after consumption of genetically modified potatoes and 0.27 mg of the 3 mg zeaxanthin dose could be detected in chylomicrons. Consumption of control potatoes had no effect on concentrations of zeaxanthin in chylomicrons. After normalization of chylomicron zeaxanthin for plasma triacylglycerol, the time course of zeaxanthin concentrations peaked at 7 h after consumption of genetically modified potatoes. There were no significant differences in the concentrations of other major potato carotenoids such as lutein and beta-carotene in chylomicrons after consumption of genetically modified and wild type control potatoes. Thus, consumption of zeaxanthin-rich potatoes significantly increases chylomicron zeaxanthin concentrations suggesting that potentially such potatoes could be used as an important dietary source of zeaxanthin.

Objective: The aim of this study was to consider the risk of micronutrient deficiencies and approaches for intervention, and to summarize existing knowledge and identify areas of ignorance., Design: Experts from a range of relevant disciplines received and considered a series of questions related to aspects of the topic., Intervention: The experts met and discussed the questions and arrived at a consensus., Conclusion: Though healthy balanced diet is available for the general European population, a few defined groups are at risk of micronutrient deficiencies. In addition, the intake of specific micronutrients such as iron, folic acid, vitamin D and vitamin B12 are often marginal. To overcome these deficiencies, either selected micronutrients or a mixture of different micronutrients might be recommended. However, to define and detect micronutrient deficiencies, specific biomarkers are only available for a few micronutrients (e. g. vitamin D, folic acid, vitamin C, iron). The definition of a risk group, based on scientific data, might be an appropriate way to justify intervention with supplements.

Background: A recent prospective cohort study revealed that moderate wine consumption but not consumption of other alcoholic beverages is associated with a decreased risk of common cold. In contrast, wine constituents such as ethanol and polyphenols are known to suppress immunity., Aim of the Study: We investigated whether acute intake of a moderate amount of alcohol modulates immune functions in healthy men and whether polyphenols in red wine with antioxidative and immunomodulatory potential induce changes in immune functions that differ from those induced by the consumption of the 12 % ethanol., Methods: Six healthy males with moderate alcohol consumption patterns randomly consumed a single dose of 500 ml of red wine (12 % ethanol), a 12 % ethanol dilution, dealcoholized red wine, and red grape juice, respectively. The following immune functions were measured before beverage consumption and 1, 3, and 24 h later: phagocytic activity and intensity of neutrophils and monocytes, production of tumor necrosis factor-alpha, interleukin-2, and interleukin-4, lymphocyte proliferation, and lytic activity of natural killer cells., Results: Acute consumption of a moderate amount of red wine and of a 12 % ethanol solution had no effect on immune functions in men. Acute consumption of polyphenol-rich beverages (dealcoholized red wine and red grape juice) also did not affect immunity., Conclusions: This study clearly shows that moderate consumption of alcohol at doses which inversely correlate with cardiovascular disease risk has no short-term effect on human immune cell functions. Acute intake of polyphenol-rich beverages such as red grape juice and dealcoholized red wine also does not affect immunity.

Background & Aims: Dietary polyphenols, including anthocyanins, are suggested to be involved in the protective effects of red wine against cardiovascular diseases. Very little data are available concerning the bioavailability of anthocyanins, major sources of red pigmentation in red wine. The aim of this study was to compare changes in plasma malvidin-3-glucoside (M-3-G), a red wine anthocyanin, and its urinary excretion after ingestion of red wine, dealcoholized red wine and red grape juice., Design: Six healthy male subjects were studied in a randomized cross over setting in a human nutrition research unit under controlled conditions. All subject consumed 500 mL of each beverage on separate days providing the following M-3-G quantities: red wine 68 mg, dealcoholized red wine 58 mg, and red grape juice 117 mg. M-3-G was measured by HPLC and photodiode detection., Results: M-3-G was found in plasma and urine after ingestion of all the beverages studied. The aglycon, sulfate or glucuronate conjugates of M-3-G were not detected in plasma and urine. Increases in plasma M-3-G concentrations were not significantly different after the consumption of either red wine or dealcoholized red wine and were about two times less than those measured after consumption of red grape juice. This difference may be caused by the about two times higher M-3-G concentration determined in red grape juice. Area under the plasma concentration curves were as follows: 288 +/- 127 nmol x h/L (red wine), 214 +/- 124nmol x h/L (dealcoholized red wine) and 662 +/- 210 nmol x h/L (red grape juice) and showed a linear relationship with the amount of anthocyanin consumed (mean +/- SD)., Conclusions: M-3-G is poorly absorbed after a single ingestion of red wine, dealcoholized red wine, or red grape juice and seems to be differentially metabolized as compared to other red grape polyphenols. Our results suggest that not anthocyanins such as M-3-G themselves but rather not yet identified anthocyanin metabolites and/or other polyphenols in red wine might be responsible for the observed antioxidant and health effects in vivo in subjects consuming red wine.